The blood plasma proteome provides a wide window into the dynamics of the protein and peptide components of human health over a lifespan. Quantitative analysis of peptide features in this window by mass spectrometry in concert with clinical diagnoses forms the basis of disease biomarker identification. Acquiring plasma biomarkers for specific cancers enables relatively cheap and noninvasive cancer screening. Inexpensive, noninvasive cancer screens are broadly applied and diagnose cancer earlier in disease progression. Earlier diagnosis is highly correlated with better treatment outcome.
The plasma proteome presents a significant challenge for fractionation technologies. The concentration of highly abundant plasma proteins and peptides exceeds the lowest abundance species by ten orders of magnitude. Detecting low abundant species in plasma in a systematic way requires a technology that enriches efficiently, has high recovery and capacity, can accommodate high loading levels, is high-throughput and can isolate multiple species from a single sample without specific protocols developed for each desired peptide.
Fractionating the plasma proteome in an unbiased way may be performed by 2D gel electrophoresis or mixed-mode (ion-exchange solid phase in-line with hydrophobic (i.e., C-18) solid phase) ultra-performance liquid chromatography (UPLC): both have reasonable enrichment but tolerate only low loading volumes. The electrophoresis method and may be pursued in parallel but has appreciable sample loss, the opposite is true for the UPLC approach. If the target if interest is known, the plasma proteome may be assayed in a directed way by solid phase extraction or counter-current chromatography. The first approach is limited by low specificity and loading volume, the second is slow, low throughput and also limited by low-loading volumes.